In conclusion, the present study shows that the FGF2 rs1048201, PDGFRB rs246395, PDGFRA rs2228230, MMP2 rs243865, and rs7201 variants may independently predict therapy failure and poor survival in non-surgically treated HNSCC patients receiving radical RT alone or combined with cisplatin-based CT. Here, PDGFRB is linked to head and neck squamous cell carcinoma.